Subthreshold Stimuli Research Articles

Two-cluster spiking activity induced by a subthreshold periodic stimulus in homogenous neuronal ensembles

We study the spiking activity of globally coupled excitable neurons in the presence of a subthreshold periodic stimulus. We find that the neuronal ensemble may spontaneous form two synchronized clusters of spiking activity, though it is impossible for an isolated neuron spiking under the same stimulus. We further reveal that the different initial states of the neurons and the coupling strength are two essential components for the onset of the two-cluster spiking activity. We finally analyze the mechanism behind the subthreshold periodic stimulus-sustained activity.

F60. Acute and chronic changes of motor network excitability in relation to the clinical benefit of pallidal stimulation in dystonia: A combined TMS and VBM study

Introduction Dystonia patients express less effective intracortical inhibition, which can potentially be restored with pallidal deep brain stimulation (DBS). The DBS-related clinical benefit in dystonia increases relatively slowly, suggesting an induction of slow plastic processes in regions involved with motor control. In our study, we explored the relationship between intracortical inhibition of the motor cortex, brain morphology, and DBS-related clinical effects. Methods Twenty-two patients (mean age 51 ± (SD)17 years) with dystonia of various distribution and etiology treated by chronic pallidal DBS and 22 healthy subjects were included in the study. Voxel-based morphometry of postoperative T1-weighted images (MPRAGE, 1 × 1 × 1 mm) was calculated for gray matter (GM) density in each voxel using CAT12/SPM12 software. Paired TMS with subthreshold conditioning stimulus followed by a supratreshold testing stimulus were applied to the motor cortex to elicit short-latency intracortical inhibition (SICI) of the motor evoked potential. The clinical effect of DBS was expressed as a change in the dystonic score (BFMDS or TWSTRS) between actual DBS ON condition and the preoperative state. Results Dystonia patients showed increased GM density in the supplementary motor area (SMA) and middle cingulate in comparison with healthy controls (p Conclusion Good responders to pallidal DBS treatment exhibited a similar level of SICI as healthy controls but non-responders were unable to increase it. Brain changes of treated patients possibly underwent grey matter rebuilding with cerebellar hypertrophy quantitatively related to the improvement of intracortical inhibition and with hypertrophy in the cortex involved in motor act preparation. All these results support the multilevel impact of effective DBS on motor networks in dystonia. Supported by the grants GACR 16-13323S.

F144. Interactions between right and left posterior parietal cortices in the left motor cortex

Introduction The posterior parietal cortices (PPCs) engage in motor processing during reach and grasp. Yet, the neural substrates behind their connections to the motor cortex (M1) are still unknown. It has been postulated that right PPC (rPPC) acts directly on left PPC (lPPC), which then acts on left M1 (lM1). Alternately, rPPC may act on lM1 circuits at the same time as lPPC. Here, we used triple-site transcranial magnetic stimulation (TMS) to test this hypothesis. Previous studies showed that rPPC or lPPC stimulation alone facilitates motor evoked potentials (MEPs), whereas rPPC and lPPC stimulation together inhibits the facilitated MEPs. To consider their interaction at M1, we tested two M1 circuits: short interval intracortical facilitation (SICF) and short interval intracortical inhibition (SICI). SICF is elicited by two suprathreshold pulses to M1 delivered in ∼ 1.5 ms intervals which facilitate M1 output. SICI inhibits M1 output and is elicited by a subthreshold conditioning stimulus delivered 1–6 ms prior to a suprathreshold pulse. We hypothesized that if rPPC and lPPC inhibit MEPs by acting on SICF or SICI in M1, a correlation would emerge. Methods 16 healthy adults participated (9 females, 22–64 years, 35.4 ± 14.6 years old). MRI-navigated TMS was delivered by 3 small coils over rPPC, lPPC and lM1. MEPs were recorded from the right first dorsal interosseous muscle. Exp 1 tested PPC-lM1 circuits and their interactions at several rPPC and lPPC stimuli intensities, including 90 and ∼ 108% RMT over lPPC and 30 to 130% RMT over rPPC. Exp 2 tested PPC-lM1 circuits and their interaction at different test MEP amplitudes of ∼ 0.2 mV, 1 mV, and 4 mV. Exp 3 tested the effect of rPPC on SICF. Exp 4 tested the effect of SICI on lPPC-lM1 and rPPC-lPPC-lM1 interactions. Results Exp 1: The interaction of rPPC and lPPC inhibited MEPs. This effect occurred when the rPPC was stimulated at 70% and 90% RMT, and the lPPC was stimulated at ∼ 108% RMT. rPPC-to-lM1 connectivity correlated with this interaction, whereas lPPC-to-lM1 connectivity did not. Exp 2: Compared to higher intensities, low intensity M1 stimulation at ∼ 0.2 mV showed facilitated rPPC-to-lM1 connectivity and increased the inhibitory effects of rPPC and lPPC interaction. Exp 3: rPPC inhibited SICF at 1.4 ± 0.1 ms, and this inhibition correlated with rPPC and lPPC inhibition. Exp 4: SICI abolished the facilitatory effect of lPPC-lM1 and the inhibitory effect of rPPC-to-lPPC-lM1 connection. SICI in the presence of lPPC-lM1 correlated with rPPC in the presence of lPPC-lM1. Conclusion We showed that the rPPC and lPPC inhibit the lM1, which is more prominent when tested at low M1 stimulation intensity. rPPC-to-lM1 connectivity correlated with this interaction. The effect of PPC on M1 may be mediated in part by cortical circuits SICF and SICI. We conclude that the effects of rPPC and lPPC likely interact at lM1.

BS18. Reduced prepulse inhibition in trigeminal neuralgia

We hypothesized that prepulse inhibition (PPI) may be decreased in trigeminal neuralgia (TN) if it leads hyperactivity of trigeminal nucleus and tested our hypothesis in a group of patients with classical TN. Consecutive nine patients with classical TN and 14 healthy subjects were enrolled in this study between January 2015 and August 2016. Diagnosis and classification were done according to the International Classification of Headache Disorders-3 (ICHD-3 beta version). Blink reflex and BR-PPI were recorded on both symptomatic and asymptomatic sides in patient group and on the right side in healthy subjects. Subthreshold conditioning stimulus was applied to the median nerve at second finger using an electrical stimulus at two different interstimulus intervals: 50 ms and 100 ms before the test stimulus to the supraorbital nerve. Standard BR recordings were normal in all groups. In healthy subjects, prepulse stimulus resulted in lower magnitude of BR-R2 (p = 0.000) and longer R2 latencies (p = 0.008) at ISIs of 50 ms and 100 ms in comparison to baseline recordings whereas no change after prepulse stimulation was observed on both symptomatic and asymptomatic sides of patients with TN. Our study provided evidence for the reduced PPI and thus, sensory gating of brainstem in classical TN. This finding was bilateral and present even on the asymptomatic side.

6. ALS disability is predicted by a shift in the balance between short latency facilitatory and inhibitory circuits

Objectives Cellular work in TDP-43 models of ALS highlight a key role for somatostatin interneuronal circuits in mediating corticomotoneuronal hyperexcitability. Previous studies in ALS patients disclosed a reduction of short interval intracortical inhibition (SICI), a biomarker of interneuronal inhibitory function. Threshold tracking transcranial magnetic stimulation (TMS) provides a non-invasive method for assessing cortical interneuronal function in the human motor cortex. Short interval intracortical facilitation (SICF) is a novel biomarker for assessing the function of excitatory cortical interneuronal circuits. The present study assessed SICI and SICF in a cohort of sporadic ALS patients to further dissect the relative contribution of excitatory and inhibitory cortical circuits in development of cortical hyperexcitability in ALS. Methods Threshold tracking TMS was used to assess motor cortical function in 25 ALS patients, with results compared to 19 healthy older controls. SICF was measured by setting the subthreshold conditioning stimulus to 95% of resting motor threshold with interstimulus intervals (ISI) between 1 and 5 ms. A concurrent measure of SICI was also made. We developed a novel “Index of Excitation” which quantified the relative contribution of inhibitory (SICI) and facilitatory (SICF) circuits in development of cortical hyperexcitability. Results Mean SICF was significantly increased in ALS patients (ALS = −18.15 ± 1.80%; controls = −8.49 ± 1.59%%, P Conclusion This study has established that cortical hyperexcitability in ALS is mediated through a combination of reduced inhibition (implying dysfunction of inhibitory circuits) and increased activity of facilitatory cortical networks. The Index of Excitability, a novel measure of corticomotoneuronal hyperexcitability, appears to predict the clinical burden of disease in ALS patients, displaying potential as a therapeutic biomarker. Strategies aimed at modulating the imbalance in cortical inhibition and excitation may prove therapeutically useful.

Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques

BackgroundShort-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear. ObjectiveTo compare T-SICI and its reliability with conventional A-SICI measurements. MethodsIn twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50–80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator. ResultsAcross the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7–0.3x, R2 = 0.99), but there was considerable interindividual variability. At CS 60–80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81–0.92) and adequate-to-excellent interday (ICC 0.61–0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17–0.42 intraday, 0.37–0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies. ConclusionThe close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique.

Noisy vestibular stimulation improves vestibulospinal function in patients with bilateral vestibulopathy.

To examine the mechanism underlying previously reported ameliorating effects of noisy galvanic vestibular stimulation (GVS) on balance performance in patients with bilateral vestibulopathy (BVP) and determine those patients (incomplete versus complete vestibular loss) that might benefit from this intervention. Vestibulospinal reflex thresholds were determined in 12 patients with BVP [2 with complete loss (cBVP) and 10 with residual function (rBVP)]. Patients were stimulated with 1Hz sinusoidal GVS of increasing amplitudes (0-1.9mA). Coherence between GVS input and stimulation-induced body motion was determined and psychometric function fits were subsequently used to determine individual vestibulospinal reflex thresholds. The procedure was repeated with an additional application of imperceptible white noise GVS (nGVS). All patients with rBVP but none with cBVP exhibited stimulation-induced vestibulospinal reflex responses with a mean threshold level of 1.26 ± 0.08mA. Additional nGVS resulted in improved processing of weak subthreshold vestibular stimuli (p = 0.015) and thereby effectively decreased the vestibulospinal threshold in 90% of patients with rBVP (mean reduction 17.3 ± 3.9%; p < 0.001). The present findings allow to identify the mechanism by which nGVS appears to stabilize stance and gait performance in patients with BVP. Accordingly, nGVS effectively lowers the vestibular threshold to elicit balance-related reflexes that are required to adequately regulate postural equilibrium. This intervention is only effective in the presence of a residual vestibular functionality, which, however, applies for the majority of patients with BVP. Low-intensity noise stimulation thereby provides a non-invasive treatment option to optimize residual vestibular resources in BVP.

Impact of sub- and supra- threshold switching in the synaptic behavior of TiO2 memristors

Al/TiO2/Au memory junctions grown by reactive sputtering were fabricated and characterized. Usual hysteretic features were obtained, spanning an order of magnitude ratio between high and low resistance states. We explored sub-threshold and supra-threshold stimuli, to describe “binary” and “analogic” synapses (i.e. synaptic emulators) characteristics in detail. We show that each type of behavior can be chosen regarding the dependence of the switching on the amplitude of voltage stimuli. The sub-threshold switching originating the analog mode is explained by the drift-diffusion of oxygen vacancies while the binary mode is attributed to the Joule-heating-assisted electric-field-induced movement of oxygen vacancies. In the supra-threshold limit we found that “excitatory” and “inhibitory” synaptic behavior can be tailored by controlling the pulsing current amplitude. We discuss this result within the artificial neural network topology framework, as changing the behavior type of the synapses results in its reconfiguration.

Enhancement of Synaptic Transmission of Sub-threshold Current Stimulus with High Rate Pulsatile Electric Stimuli in a Recurrent Neuron Model

Enhancement of Synaptic Transmission of Sub-threshold Current Stimulus with High Rate Pulsatile Electric Stimuli in a Recurrent Neuron Model

Long-latency interhemispheric interactions between motor-related areas and the primary motor cortex: a dual site TMS study

The primary motor cortex (M1) is highly influenced by premotor/motor areas both within and across hemispheres. Dual site transcranial magnetic stimulation (dsTMS) has revealed interhemispheric interactions mainly at early latencies. Here, we used dsTMS to systematically investigate long-latency causal interactions between right-hemisphere motor areas and the left M1 (lM1). We stimulated lM1 using a suprathreshold test stimulus (TS) to elicit motor-evoked potentials (MEPs) in the right hand. Either a suprathreshold or a subthreshold conditioning stimulus (CS) was applied over the right M1 (rM1), the right ventral premotor cortex (rPMv), the right dorsal premotor cortex (rPMd) or the supplementary motor area (SMA) prior to the TS at various CS-TS inter-stimulus intervals (ISIs: 40–150 ms). The CS strongly affected lM1 excitability depending on ISI, CS site and intensity. Inhibitory effects were observed independently of CS intensity when conditioning PMv, rM1 and SMA at a 40-ms ISI, with larger effects after PMv conditioning. Inhibition was observed with suprathreshold PMv and rM1 conditioning at a 150-ms ISI, while site-specific, intensity-dependent facilitation was detected at an 80-ms ISI. Thus, long-latency interhemispheric interactions, likely reflecting indirect cortico-cortical/cortico-subcortical pathways, cannot be reduced to nonspecific activation across motor structures. Instead, they reflect intensity-dependent, connection- and time-specific mechanisms.

Spatially coincident vibrotactile noise improves subthreshold stimulus detection.

Stochastic Resonance (SR) is a phenomenon, mainly present in nonlinear detection systems, in which the addition of certain amount of noise, called optimal noise, has proven to enhance detection performance of subthreshold stimuli. When added noise is present only during the stimulus, an additional enhancement can be reached. This phenomenon was called time Coincidence Enhanced Stochastic Resonance (CESR). The aim of this study was to study the effect of spatially distributed vibrotactile noise in subthreshold stimuli detection. The correct response rates from two different stimuli conditions were compared, using four tactile stimulator systems to excite four different spatial locations on the fingertip. Under two different conditions, the stimuli were present in only one randomly chosen stimulator. For the first condition, all stimulators contain optimal noise level. In the second condition, the optimal noise was present only at the stimulator with the stimulus. SR threshold principle should not produce different correct response rates between the two conditions, since in both cases the noise enables the subthreshold stimulus to go above threshold. The stimulus signal used was a rectangular displacement controlled pulse that lasted 300ms within a 1.5s attention interval, applied to the exploratory zone of the index finger of 13 human subjects. For all subjects it was found that detection rates were better (p<0.0003) when noise was spatially coincident with the stimulus, compared to the condition in which noise was present simultaneously in all the stimulators. According to our literature review this is the first report of SR being influenced by the spatial location of the noise. These results were not found previously reported, so represent the discovery of a new phenomenon. We call this phenomenon Spatial-Coincidence-Enhanced Stochastic Resonance (SCESR). As results show, the optimal noise level is dependent on the relative position between stimulus and noise.

P226 The effect of interstimulus interval between the conditioning and test stimulus on inhibition and fascilitation: A transcranial magnetic stimulation study

Objective Transcranial magnetic stimulation (TMS) technique creates small and temporary electrical current on cerebral cortex via a strong magnetic field. Previous studies investigating the cortical excitability using paired pulse stimulation technique have implemented a suprathreshold test stimulus (TS) conditioned by subthreshold stimulus (CS). If interstimulus interval (ISI) between CS and TS is 1–6 ms, motor evoked potential (MEP) amplitude will decrease and it is called short interval intracortical inhibition (SICI). However, if ISI between two stimuli is 7–30 ms, MEP amplitude will increase and it is called intracortical fascilitation (ICF). In this study, we investigate the effect of different ISI values on inhibition and excitation. Methods Resting motor threshold (rMT), MEP amplitude, SICI and ICF was studied in thirthy healthy subjects. MEP amplitude was recorded with 120% of rMT. CS and TS was arranged as 80% rMT and 120% of rMT respectively. During SICI studies, 2 ms and 3 ms ISI was compared to each other. On the other hand 10 ms and 12 ms ISI were studied for ICF. Results There was more prominent inhibition using 3 ms ISI than 2 ms ISI. More prominent facilitation was observed with 12 ms ISI than 10 ms ISI. Discussion For time saving, 3 ms ISI and 12 ms ISI might be preferred to obtain better inhibition and facilitation during SICI and ICF studies respectively.

P252 Prepulse inhibition of blink reflex after different types of somatosensory stimuli

Objective Prepulse inhibition (PPI) is a neurophysiological method in which inhibition of a reflex response occurs when a preceding stimulus is applied. It is generally created by digital somatosensory stimulation. R2 magnitude gets reduced using certain interstimulus intervals (ISIs) whereas short ISI leads to facilitation of R1. We aimed to analyze the changes of BR-PPI using digital somatosensory stimulation and mixed nerve stimulation at wrist. Patients and method We included 18 healthy subjects (38.8 ± 10.9 years, 12 women) and performed BR investigations after unconditioned and conditioned supraorbital electrical stimuli. For conditioned stimuli, we applied two different preceding subthreshold somatosensory stimuli: i. stimulation of second finger, ii. stimulation of median nerve at wrist. Three different ISIs (50, 100, 300 ms) were used for each type of stimulation. Presence and extent of alteration after each conditioning stimulus were compared. Results R2 area significantly reduced after each conditioning stimulus at each ISI. R2 latency was longer at ISIs of 100 and 300 ms whereas R1 magnitude was higher at all ISIs. However, the increase in R1 magnitude was more pronounced at ISIs of 50 and 100 ms. Conclusions Our results clearly show that both digital somatosensory and mixed nerve stimulations lead to inhibition of R2 area and facilitation of R1 magnitude. Therefore, both stimulations and both techniques are comparable.

P244 Normal cortical modulation of subcortical structures is altered in cervical dystonia

Objective Blink reflex (BR) is obtained after different kinds of stimuli, such as trigeminal supraorbial branch stimulation (trigeminal BR, TBR) or median nerve stimulation at wrist (hand-evoked BR, HBR). Inhibition of TBR occurs when a preceding subthreshold stimulus is applied before trigeminal stimulation (prepulse inhibition, PPI). In healthy subjects, magnitude of HBR is increased and magnitude of PPI of TBR is decreased if the stimulated hand is positioned in the peripersonal space (PPS). Here, we aimed to investigate the changes of HBR and PPI of the TBR in PPS to understand alterations of cortical modulations of subcortical structures in cervical dystonia. Patients and method We recruited 23 consecutive patients with idiopathic CD and 21 healthy subjects. All participants had HBR and age and gender were similar between groups. HBR and PPI of the TBR were recorded while stimulated hand was in the extrapersonal space (far condition) and in the PPS (near condition). Baseline values were compared between patient with CD and healthy subjects. Further comparisons were done between far and near conditions. Results Magnitude of baseline HBR was bigger in patients with CD compared to healthy subjects. The magnitude further increased in healthy subjects whereas it was reduced in patients with CD. In healthy subjects, prepulse stimulation led to the reduced magnitude of R2 component of BR under far condition whereas the reduction was less evident under near condition. Although prepulse inhibition was low in patients with CD compared to healthy subjects, the reduction was more evident under near condition in patients with CD. Discussion Enhancement of HBR and attenuation of PPI of the TBR in the PPS is a normal phenomenon that provides evidence for top-down modulation of the neural circuitry underlying these reflexes. In CD, these normal alterations are lost which suggest abnormal modulation of higher-order centers.

The influence of vibratory stimulus using stochastic resonance on static posture control ability of senior adults

Purpose The purpose of the study was to investigate the effect of vibratory stimulus on the static postural control of 8 healty senior adults. Methods To achieve this goal, all subjects participated in two different kinds of static postural control tasks. Task 1 was a static postural control task, where both-legs stand on the ground. Second task was an unstable static postural control task using only single leg stance. As they maintain their balance, 6 different vibratory stimulus were provided on the sole of their feet(personal threshold 0%, 80%, 90%, 100%, 110%, 120%). Results The results of the study were as follows: First, there was no significant differences in postural control ability according to different types of vibrator intensity. Second, there was a significant difference in single-leg postural control ability according to vibrator intensity. Third, there was a significant difference in anterio-posterior stability according to the different types of vibrator intensity. Conclusion Stochastic resonance using vibratory stimulus was more effective in the single leg stance task, rather than the double leg stance task. Moreover, sub-threshold vibratory stimulus(80%, 90%) intensity were more effective than higher vibratory stimulus(100%, 110%, 120%).

Alpha-Band Brain Oscillations Shape the Processing of Perceptible as well as Imperceptible Somatosensory Stimuli during Selective Attention.

Attention filters and weights sensory information according to behavioral demands. Stimulus-related neural responses are increased for the attended stimulus. Does alpha-band activity mediate this effect and is it restricted to conscious sensory events (suprathreshold), or does it also extend to unconscious stimuli (subthreshold)? To address these questions, we recorded EEG in healthy male and female volunteers undergoing subthreshold and suprathreshold somatosensory electrical stimulation to the left or right index finger. The task was to detect stimulation at the randomly alternated cued index finger. Under attention, amplitudes of somatosensory evoked potentials increased 50-60 ms after stimulation (P1) for both suprathreshold and subthreshold events. Prestimulus amplitude of peri-Rolandic alpha, that is mu, showed an inverse relationship to P1 amplitude during attention compared to when the finger was unattended. Interestingly, intermediate and high amplitudes of mu rhythm were associated with the highest P1 amplitudes during attention and smallest P1 during lack of attention, that is, these levels of alpha rhythm seemed to optimally support the behavioral goal ("detect" stimuli at the cued finger while ignoring the other finger). Our results show that attention enhances neural processing for both suprathreshold and subthreshold stimuli and they highlight a rather complex interaction between attention, Rolandic alpha activity, and their effects on stimulus processing.SIGNIFICANCE STATEMENT Attention is crucial in prioritizing processing of relevant perceptible (suprathreshold) stimuli: it filters and weights sensory input. The present study investigates the controversially discussed question whether this attention effect extends to imperceptible (subthreshold) stimuli as well. We found noninvasive EEG signatures for attentional modulation of neural events following perceptible and imperceptible somatosensory stimulation in human participants. Specifically, stimulus processing for both kinds of stimulation, subthreshold and suprathreshold, is enhanced by attention. Interestingly, Rolandic alpha rhythm strength and its influence on stimulus processing are strikingly altered by attention most likely to optimally achieve the behavioral goal.

Low-Frequency Cortical Oscillations Entrain to Subthreshold Rhythmic Auditory Stimuli

Many environmental stimuli contain temporal regularities, a feature that can help predict forthcoming input. Phase locking (entrainment) of ongoing low-frequency neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism for enhancing neuronal responses and perceptual sensitivity, by aligning high-excitability phases to events within a stimulus stream. Previous experiments show that rhythmic structure has a behavioral benefit even when the rhythm itself is below perceptual detection thresholds (ten Oever et al., 2014). It is not known whether this "inaudible" rhythmic sound stream also induces entrainment. Here we tested this hypothesis using magnetoencephalography and electrocorticography in humans to record changes in neuronal activity as subthreshold rhythmic stimuli gradually became audible. We found that significant phase locking to the rhythmic sounds preceded participants' detection of them. Moreover, no significant auditory-evoked responses accompanied this prethreshold entrainment. These auditory-evoked responses, distinguished by robust, broad-band increases in intertrial coherence, only appeared after sounds were reported as audible. Taken together with the reduced perceptual thresholds observed for rhythmic sequences, these findings support the proposition that entrainment of low-frequency oscillations serves a mechanistic role in enhancing perceptual sensitivity for temporally predictive sounds. This framework has broad implications for understanding the neural mechanisms involved in generating temporal predictions and their relevance for perception, attention, and awareness.SIGNIFICANCE STATEMENT The environment is full of rhythmically structured signals that the nervous system can exploit for information processing. Thus, it is important to understand how the brain processes such temporally structured, regular features of external stimuli. Here we report the alignment of slowly fluctuating oscillatory brain activity to external rhythmic structure before its behavioral detection. These results indicate that phase alignment is a general mechanism of the brain to process rhythmic structure and can occur without the perceptual detection of this temporal structure.

Modeling electrical stimulation of retinal ganglion cell with optimizing additive noises for reducing threshold and energy consumption

BackgroundEpiretinal prosthesis is one device for the treatment of blindness, which target retinal ganglion cells (RGCs) by electrodes on retinal surface. The stimulating current of epiretinal prosthesis is an important factor that influences the safety threshold and visual perception. Stochastic resonance (SR) can be used to enhance the detection and transmission of subthreshold stimuli in neurons. Here, it was assumed that SR was a potential way to improve the performance of epiretinal prosthesis. The effect of noises on the response of RGCs to electrical stimulation and the energy of stimulating current was studied based on a RGC model.MethodsThe RGC was modeled as a multi-compartment model consisting of dendrites and its branches, soma and axon. To evoke SR, a subthreshold signal, a series of bipolar rectangular pulse sequences, plus stochastic biphasic pulse sequences as noises, were used as a stimulus to the model. The SR-type behavior in the model was characterized by a “power norm” measure. To decrease energy consumption of the stimulation waveform, the stochastic biphasic pulse sequences were only added to the cathode and anode phase of the subthreshold pulse and the noise parameters were optimized by using a genetic algorithm (GA).ResultsWhen certain intensity of noise is added to the subthreshold signal, RGC model can fire. With the noise’s RMS amplitudes increased, more spikes were elicited and the curve of power norm presents the inverted U-like graph. The larger pulse width of stochastic biphasic pulse sequences resulted in higher power norm. The energy consumption and charges of the single bipolar rectangular pulse without noise in threshold level are 468.18 pJ, 15.30 nC, and after adding optimized parameters’s noise to the subthreshold signal, they became 314.8174 pJ, 11.9281 nC and were reduced by 32.8 and 22.0%, respectively.ConclusionsThe SR exists in the RGC model and can enhance the representation of RGC model to the subthreshold signal. Adding the stochastic biphasic pulse sequences to the cathode and anode phase of the subthreshold signal helps to reduce stimulation threshold, energy consumption and charge of RGC stimulation. These may be helpful for improving the performance of epiretinal prosthesis.

P065 Abnormally low intracortical inhibition in dystonia with poor response to pallidal stimulation

Introduction Pallidal stimulation (GPi DBS) is an effective treatment of dystonic syndromes with a relatively high variability of clinical benefit. As patients with dystonia typically have a lower ability to suppress unwanted movements, we expected a decreased intracortical inhibition of motor cortex, which can be potentially reversed by GPi DBS. Objectives To distinguish between patients with dystonia according to the clinical outcome of GPi DBS using short-latency intracortical inhibition (SICI) of the motor cortex assessed by paired transcranial magnetic stimulation (TMS). Patients & methods We examined 22 patients (mean age 51 ± 17 years) with dystonia of various distribution and origin treated by GPi DBS in different time intervals from implantation. Paired TMS with subthreshold conditioning stimulus followed by a supratreshold testing stimulus 2.5 ms later were applied to the motor cortex to elicit SICI in GPi DBS ON and GPi DBS OFF condition two hours later. The clinical effect (CE) was expressed as a change in the dystonic score (Burke-Fahn-Marsden Dystonia rating Scale or Toronto Western Spasmodic Torticollis Scale) between actual GPi DBS ON condition and the preoperative state. Results The SICI was less effective in patients than in controls regardless of the ON and OFF conditions (p Download : Download high-res image (206KB) Download : Download full-size image ). Non-responders (n = 9; 50% CE, p Download : Download high-res image (225KB) Download : Download full-size image Fig. 2a) and in addition, the shortest MEP onset latency was observed in non-responders (p Conclusions Our results suggest that the best responders to GPi DBS treatment exhibited a similar level of SICI as in healthy controls. On the contrary, non-responders were unable to increase their reduced cortical inhibition and effectively suppressed dystonic symptoms. We speculate that decreased intracortical inhibition with abnormally fast transmission volley is underpinned by the poor complexity of the motor network. Supported by the grant IGA MZ CR NT12282-5/2011.

Random Noise Stimulation of the Cortex: Stochastic Resonance Enhances Central Mechanisms of Perception

It has been demonstrated that detection thresholds decrease by adding random noise to the peripheral nervous system (Simonotto et al., 1996, Collins et al., 1996) in accordance to a stochastic resonance (SR) phenomenon. Psychophysical experiments in humans suggest that SR in the visual system can occur in the primary visual cortex (Aihara et al., 2008). In an EEG (electroencephalography) study in humans, it was shown that when a small amount of tactile random noise was applied to a tactile signal on the fingertip signal-to-noise ratio of the EEG signals decreased for the optimal level of peripheral noise, which is a characteristic of SR (Manjarrez et al., 2003). In previous work, signal and noise were always applied to the peripheral nervous system and not directly to the central nervous system. The question arises as to whether SR-like behavior occurs if noise is added to cortical areas. Here subjects performed a visual perception task while different levels of noise were added either to the peripheral or central nervous system. Peripheral noise was zero-mean Gaussian noise represented on the screen. Central noise was applied via transcranial random noise stimulation (tRNS, 100-640 Hz, intensity varying between 0 and 1.5 mA) with one electrode overlying the visual cortex. Our results indicate that a small amount of peripheral as well as central noise induces a SR effect for sub-threshold stimuli, i.e. the detection threshold is reduced for optimal noise levels. Increasing the noise beyond the optimal amount does not benefit perception.